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Background: Prognostic factors in adolescent and young adult (AYA) glioma are not well understood. Though clinical and molecular differences between pediatric and adult glioma have been characterized, their application to AYA populations is less clear. There is a major need to develop more robust evidence-based practices for managing AYA glioma patients., Methods: A systematic review using PRISMA methodology was conducted using multiple databases with the objective of identifying demographic, clinical, molecular and treatment factors influencing AYA glioma outcomes., Results: 40 Studies met inclusion criteria. Overall survival was highly variable across studies depending on glioma grade, anatomic compartment and cohort characteristics. Thirty-five studies suffered from high risk of bias in at least one domain. Several studies included older adults within their cohorts; few captured purely AYA groups. Despite study heterogeneity, identified favorable prognosticators included younger age, higher functional status at diagnosis, low-grade pathology, oligodendroglioma histology and increased extent of surgical resection. Though isocitrate dehydrogenase (IDH) mutant status was associated with favorable prognosis, validity of this finding within AYA was compromised though may studies including older adults. The prognostic influence of chemotherapy and radiotherapy on overall survival varied across studies with conflicting evidence., Conclusion: Existing literature is heterogenous, at high risk of bias, and rarely focused solely on AYA patients. Many included studies did not reflect updated pathological and molecular AYA glioma classification. The optimal role of chemotherapy, radiotherapy, and targeted agents cannot be determined from existing literature and should be the focus of future studies., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Pediatric hemorrhagic stroke (HS) accounts for a large proportion of childhood strokes, 1 of the top 10 causes of pediatric deaths. Morbidity and mortality lead to significant socio-economic and psychosocial burdens. To understand published data on recognizing and managing children with HS, we conducted a systematic review of the literature presented here. We searched PubMed, Embase, CINAHL and the Cochrane Library databases limited to English language and included 174 studies, most conducted in the USA (52%). Terminology used interchangeably for HS included intraparenchymal/intracranial hemorrhage, spontaneous ICH, and cerebrovascular accident (CVA). Key assessments informing prognosis and management included clinical scoring (Glasgow coma scale), and neuroimaging. HS etiologies reported were systemic coagulopathy (genetic, acquired pathologic, or iatrogenic), or focal cerebrovascular lesions (brain arteriovenous malformations, cavernous malformations, aneurysms, or tumor vascularity). Several scales were used to measure outcome: Glasgow outcome score (GOS), Kings outcome score for head injury (KOSCHI), modified Rankin scale (mRS) and pediatric stroke outcome measure (PSOM). Most studies described treatments of at-risk lesions. Few studies described neurocritical care management including raised ICP, seizures, vasospasm, or blood pressure. Predictors of poor outcome included ethnicity, comorbidity, location of bleed, and hematoma >2% of total brain volume. Motor and cognitive outcomes followed independent patterns. Few studies reported on cognitive outcomes, rehabilitation, and transition of care models. Interdisciplinary approach to managing HS is urgently needed, informed by larger cohort studies targeting key clinical question (eg development of a field-guide for the clinician managing patients with HS that is reproducible internationally)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Medulloblastoma is a rare diagnosis among adolescents and young adults (AYA). Though prognostic factors and treatment are well characterized among children with medulloblastoma, equivalent data for AYA are sparse. We conducted a systematic review to identify predictors of survival among AYA with medulloblastoma., Methods: We searched for primary studies of AYA (age 15-39 at diagnosis) with medulloblastoma in high-income countries within OVID MEDLINE, EMBASE, and EBM Reviews-Cochrane library databases from inception to August 2020. Patient demographics, primary outcomes, and univariate and multivariable data on all prognostic factors were collected from included studies. Prognosticators were characterized as patient, disease, or treatment-related., Results: We identified 18 articles. 5-year overall survival ranged between 40% and 89%, while disease-free survival ranged from 49% to 89%. Study quality was low as assessed by the Quality in Prognostic factor Studies tool. Though meta-analyses were not possible due heterogeneity, narrative summaries suggested that lower disease burden, superior postoperative functional status, and higher doses and larger fields of radiation were associated with improved survival. Reported chemotherapy regimens were heterogeneous in timing, agents, and relationship with radiation, precluding meaningful comparisons. Only one study included molecular subgroups for analysis, with the majority (76.5%) of tumors classified as Sonic Hedgehog (SHH)., Conclusions: Prognostication and treatment of AYA medulloblastoma is limited by a dearth of primary evidence and lack of specificity for patients aged 15-39. Dedicated prospective trials to delineate the benefit of various chemotherapy and radiation regimens are required in this population to identify prognosticators and ideal treatment regimens., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with substantial health care utilization and burden on families. Little is known about health care utilization during specific treatment phases., Procedures: We identified children with ALL diagnosed during 2002-2012 in Ontario, Canada and treated according to Children's Oncology Group (COG) protocols. Disease and treatment data were chart abstracted. Population-based health care databases identified all outpatient visits, emergency department (ED) visits, and hospitalizations. In addition to comparing standard and intensified versions of treatment phases, we compared patients receiving different steroids (dexamethasone vs. prednisone) and different versions of interim maintenance (IM) (Capizzi vs. high-dose methotrexate [HD-MTX])., Results: Six hundred thirty-seven children met inclusion criteria. During intensified consolidation, 76.2% of patients were hospitalized at least once, compared to only 32.3% of patients receiving standard consolidation (p < .0001). Similarly, 72.9% of patients receiving intensified delayed intensification (DI) were hospitalized during this phase compared to 50.3% of patients receiving standard DI (p < .0001). Among patients receiving a four-drug induction, those receiving dexamethasone had an 85% higher rate of ED visits (adjusted rate ratio [aRR] 1.85, 95th confidence interval [95CI] 1.14-3.00; p = .01) and a 44% higher rate of hospitalization (aRR 1.44, 95CI 1.24-1.68) compared to those receiving prednisone. Among high-risk B-ALL and T-ALL patients in IM, Capizzi MTX was not associated with an increased rate of ED visits versus HD-MTX., Conclusions: These results can be used to inform anticipatory guidance for families, particularly those undergoing intensified therapy. Our results also suggest that increased toxicity rates associated with dexamethasone during Induction seen in clinical trials reflect real-world practice., (© 2021 Wiley Periodicals LLC.)

Background: Although different treatment protocols for childhood acute lymphoblastic leukaemia (ALL) all achieve high cure rates, their health care utilisation and costs have not been rigorously compared., Methods: Disease, treatment, and outcome data were chart abstracted for all children with ALL in Ontario, Canada, diagnosed 2002-2012. Linkage to population-based databases identified health care utilisation. Utilisation-associated costs were determined through validated algorithms. Chemotherapy-associated costs were calculated separately. Health care utilisation and costs were compared between patients receiving Children's Oncology Group (COG) versus Dana-Farber Cancer Institute (DFCI)-based treatment., Findings: Of 802 patients, 146 (18.2%) were treated on DFCI-based protocols. COG patients experienced significantly higher rates of emergency department (ED) visits (adjusted rate ratio [aRR]: 1.3, 95% confidence interval [CI]: 1.1-1.5; p = 0·01), whereas outpatient visit rates were 60% higher among DFCI patients (aRR: 1.6, 95% CI: 1.5-1.7, p < 0.0001). In adjusted analyses, DFCI-associated cost intensity was 70% higher (aRR: 1.7, 95% CI: 1.5-1.9; p < 0.0001), mainly attributable to outpatient visit costs. Total chemotherapy costs were higher among COG-treated patients ($39,400 ± $1100 versus $33,400 ± $2800; p = 0.02). Among PEG-ASNase-treated patients, total chemotherapy costs were highest among DFCI patients (median $54,200 ± $7400; p = 0.003 versus COG patients)., Interpretation: COG and DFCI treatments were associated with higher ED visit rates and higher outpatient visit rates, respectively. Overall utilisation-associated costs were increased in DFCI-treated patients. Administration of some intravenous chemotherapy at home and decreases in PEG-ASNase cost would decrease health care utilisation and costs for all patients and mitigate differences between COG and DFCI protocols., Funding: C 17 Research Network., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SG has consulted for Jazz Pharmaceuticals. All other authors declare no relevant conflicts of interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Although a cancer diagnosis during the adolescent and young adult (AYA) years is a traumatic event, and psychiatric disorders generally manifest during the AYA period, the impact of a cancer diagnosis on long-term mental health outcomes in this population is not well characterized. We conducted a systematic review and meta-analysis to determine if survivors of AYA cancers are more likely to develop psychiatric disorders. A systematic literature search of five databases, MEDLINE, CINAHL, Web of Science, EMBASE, and PsycINFO, was conducted from their inception to November 2018. The outcome measures were psychiatric disorders as per the Diagnostic Statistical Manual criteria, or psychiatric medication use. Study eligibility, appraisal, and data abstraction were independently conducted by two reviewers. Of 7934 total studies, four met eligibility criteria for the systematic review, three of which were included in the meta-analysis. Compared to cancer-free controls, survivors were at an elevated risk of mood disorders (odds ratio [OR] 1.36; 95% CI 1.19-1.55) and anxiety disorders (OR 1.16; 95% CI 1.05-1.28), but not substance-related disorders, (OR 0.88; 95% CI 0.63-1.22). The most commonly identified risk factors were the female sex and older age at diagnosis. We found higher odds of anxiety and mood disorders in AYA-onset cancer survivors. However, few AYA-specific studies currently exist that analyze psychiatric disorders using consistent and standardized methods. Additional studies confirming these findings are warranted.

Introduction: A major barrier to improving childhood cancer survival is the perception that paediatric oncology services are too costly for low-income and middle-income country (LMIC) health systems. We conducted a systematic review to synthesise existing evidence on the costs and cost-effectiveness of treating childhood cancers in LMICs., Methods: We searched multiple databases from their inception to March 2019. All studies reporting costs or cost-effectiveness of treating any childhood cancer in an LMIC were included. We appraised included articles using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Where possible, we extracted or calculated the cost per disability-adjusted life year (DALY) averted using reported survival and country-specific life expectancy. Cost/DALY averted was compared with per capita gross domestic product (GDP) as per WHO-Choosing Interventions that are Cost-Effective guidelines to determine cost-effectiveness., Results: Of 2802 studies identified, 30 met inclusion criteria. Studies represented 22 countries and nine different malignancies. The most commonly studied cancers were acute lymphoblastic leukaemia (n=10), Burkitt lymphoma (n=4) and Wilms tumour (n=3). The median CHEERS checklist score was 18 of 24. Many studies omitted key cost inputs. Notably, only 11 studies included healthcare worker salaries. Cost/DALY averted was extracted or calculated for 12 studies and ranged from US$22 to US$4475, although the lower-end costs were primarily from studies that omitted key cost components. In all 12, cost/DALY averted through treatment was substantially less than country per capita GDP, and therefore considered very cost-effective., Conclusion: Many included studies did not account for key cost inputs, thus underestimating true treatment costs. Costs/DALY averted were nonetheless substantially lower than per capita GDP, suggesting that even if all relevant inputs are included, LMIC childhood cancer treatment is consistently very cost-effective. While additional rigorous economic evaluations are required, our results can inform the development of LMIC national childhood cancer strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Many survivors of childhood cancer are at high risk of late effects of their cancer therapy, including cardiac toxicity and subsequent malignant neoplasms (SMN). Current North American guidelines recommend periodic surveillance for these late effects. We conducted a systematic review of the literature to estimate rates of adherence to recommended surveillance and summarize studies evaluating interventions intended to increase adherence., Methods: We searched MEDLINE, Embase, Web of Science, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) for articles published between January 2000 and September 2018 that reported adherence to surveillance for cardiac toxicity and SMN (breast and colorectal cancer) and interventions implemented to improve completion of recommended testing. Risk of bias was assessed using relevant Cochrane checklists. Due to heterogeneity and overlapping study populations, we used narrative synthesis to summarize the findings. This review was registered in PROSPERO: CRD42018098878., Results: Thirteen studies met our inclusion criteria for assessing adherence to surveillance, while five assessed interventions to improve rates of surveillance. No studies met criteria for low risk of bias. Completion of recommended surveillance was lowest for colorectal cancer screening (11.5-30.0%) followed by cardiomyopathy (22.3-48.1%) and breast cancer (37.0-56.5%). Factors such as patient-provider communication, engagement with the health care system, and receipt of information were consistently reported to be associated with higher rates of surveillance. Of five randomized controlled trials aimed at improving surveillance, only two significantly increase completion of recommended testing-one for echocardiography and one for mammography. Both involved telephone outreach to encourage and facilitate these tests., Conclusion: The majority of childhood cancer survivors at high risk of cardiac toxicity or SMN do not receive evidence-based surveillance. There is paucity of rigorous studies evaluating interventions to increase surveillance in this population., Implications for Cancer Survivors: Robust trials are needed to assess whether tailored interventions, designed based on unique characteristics and needs of each survivor population, could improve adherence.

Background: For parents, a diagnosis of cancer in their child is a traumatic experience. However, there is conflicting evidence about the risk of developing mental illness among parents following diagnosis. Our objective was to conduct a meta-analysis to determine the prevalence of mental illness in parents of children with cancer., Methods: Four databases were searched to identify articles describing the prevalence of anxiety, depression, or posttraumatic stress disorder (PTSD) in parents of pediatric cancer patients. Two reviewers independently screened and extracted data. Subgroup analyses by gender and phase of cancer experience were selected a priori. Studies were reviewed in accordance with PRISMA guidelines., Results: Of 11 394 articles identified, 58 met inclusion criteria. Reported prevalence was highly heterogeneous, ranging from 5% to 65% for anxiety (pooled prevalence 21% [95% CI, 13%-35%]), 7% to 91% for depression (pooled prevalence 28% [95% CI, 23%-35%]), and 4% to 75% for PTSD (pooled prevalence 26% [95% CI, 22%-32%]). Prevalence was consistently higher than noncancer parental controls. Heterogeneity was not explained by parental gender or child's cancer phase and was instead likely due to significant methodological differences in measurement tools and defined thresholds., Conclusions: Parents of children with cancer have a higher prevalence of anxiety, depression, and PTSD compared with population controls. Yet, the reported prevalence of mental illness was highly variable, hampering any conclusive findings on absolute prevalence. To better understand the risk of long-term mental illness in this population and target interventions, future studies must adhere to standardized reporting and methods., (© 2019 Wiley Periodicals, Inc.)